L0301P8 - Fuel Molecules Part 2
__TOC__ Pyruvate Oxidation *Pyruvate + NAD+ + CoA —> acetyl CoA + NADH + H+ + CO2 *occurs under aerobic conditions *where pyruvate from glycolysis is converted to acetyl CoA in order to enter the Citric Acid Cycle Citric Acid Cycle/ Krebs Cycle *occurs in the mitochondrial matrix *Start: acetyl CoA **can come from glycolysis, fatty acid metabolism etc *regulated by acetyl CoA and electron carriers (must in the reoxidised form) *is necessary to occur for the electron transport chain to occur Process *8 steps in total *key steps: **step 1: acetyl CoA —> 6C (citrate) **steps 3, 4 and 8: NAD+ —> NADH **step 5: GDP + Pi —> GTP **step 6: FAD —> FADH2 **step 8: results in 4C oxaloacetate Results *from each acetyl CoA **2 CO2 **3 NADH **1 FADH2 **1 ATP (actually 1 GTP which gets converted to ATP) Oxidative Phosphorylation *the technical reaction name for how cells produce energy *two methods: **electron transport chain (ETC) **chemiosmosis ***energy derived from electron transfer reactions is temporarily stored as a transmembrane difference in charge and pH which subsequently drives the formation of ATP in oxidative phosphorylation Mitochondria *double membraned *inner membrane: **has many proteins involved in metabolic processes ** is less permeable than outer membrane *mitochondrial matrix has enzymes and chemical intermediates involved in energy production *contains DNA ATP synthase *molecular machine/motor - subunit rotates exposing the active site for ATP synthesis *the proton-motive force (action potential) causes protons to diffuse back into the mitochondrial interior through the membrane channel protein ATP synthase *diffusion is coupled with the production of ATP Uncoupling of Mitochondria *there are some cells in which electron transfer (and thus proton gradient) is not coupled with the synthesis of ATP *e.g. brown fat cells **a protein, thermogenin, provides protons with an alternative pathway to the matrix **heat is produced instead of ATP **this mechanism is used to keep vital organs warm in newborns Inhibitors of Respiration *many poisons (e.g. cyanide) interfere with the complexes of the ETC *others can also interfere with ATP synthase *both cases lead to no production of ATP What if something goes wrong? Deprivation of Oxygen in Tissues - Hypoxia *ETC is inhibited = level of ATP decreases *anaerobic glycolysis activated *lactic acid levels increases, intracellular pH decreases *pH change all affect protein strucutre, water flow = hypoxic cells swell *enzymes leak through the membrane and lead to cell death *very important in organ transplants Disfunction in Oxidative Phosphorylation *Leigh Disease *severe lactic acidosis *neurological abnormalities and death Inhalation of Hydrogen Cyanide or Ingestion of Potassium Cyanide *inhibition of ETC *tissue asphyxia, particularly of the CNS Electron Transport Chain *also known as the respiratory chain *oxidation of NADH and FADH2 (regenerates NAD+, FAD) *step in which most ATP is produced **produces H2O and up to 28 ATP *occurs in the inner membrane of the mitochondria *cannot occur if oxygen is not present as electrons will get stuck in the complexes *involves 4 large complexes **are integral proteins **contain electron carriers and enzymes **each of which hold donated electrons tighter and with greater affinity than the previous carrier in the chain Process of NADH #NADH donates its electrons to the first carrier - NADH-Q reductase #NADH gets converted back to NAD+ #Protons are pumped across the membrane into the intermembrane space #Electrons are passed onto a mobile molecule called ubiquinone (lipid) #Ubiquinone passes electrons to cytochrome C reductase = more protons to be pumped across the membrane #Cytochrome C reductase reduces the carrier, cytochrome C passing on the electrons #Cytochrome C oxidase oxidises the cytochrome C to take the electrons causing more protons to be pumped across the membrane #Oxygen then takes up the electrons and two protons to form water #The intermembrane space is now more positively charged than the matrix - potential energy #Protons flow down the concentration gradient through the channel of the last protein, ATP synthase #ADP and Pi join to form ATP Process for FADH2 #While complex 1 accepts electrons from NADH, complex 2 - succinate dehydrogenase - accepts electrons for FADH2 #Ubiquinone carries electrons from complex 2 to complex 3 #Rest of the process is the same as it is for NADH